Tethering of the IgG1 Antibody to Amorphous Silica for Immunosensor Development: A Molecular Dynamics Study

Abstract

A key factor for improving the sensitivity and performance of immunosensors based on mechanical-plasmonic methods is the orientation of the antibody proteins immobilized on the inorganic surface. Although experimental techniques fail to determine surface phenomena at the molecular level, modern simulations open the possibility of improving our understanding of protein-surface interactions. In this work, Replica Exchange Molecular Dynamics (REMD) simulations have been used to model the IgG1 protein tethered on amorphous silica surface considering a united-atom model and a relatively large system (2500 nm 2 surface). Additional Molecular Dynamics (MD) simulations have been conducted to derive an atomistic model for the amorphous silica surface using the cristobalite crystal structure as starting point and to examine the structure of the free IgG1 antibody in solution for comparison when immobilized. Analyses of the trajectories obtained for the tethered IgG1, which was sampled considering 32 different temperatures, have been used to define the geometry of the protein with respect to the inorganic surface. The tilt angle of the protein with respect to the surface plane increases with the temperature, the most populated value being 24º, and 66º and 87º at the lowest (250 K), room (298 K) and highest (380 K) temperature. This variation indicates that the importance of proteinsurface interactions decreases with increasing temperature. The influence of the surface on the structure of the antibody is very significant in the constant region, which is directly involved in the tethering process, while it is relatively unimportant for the antigen-binding fragments, which are farthest from the surface. These results are expected to contribute to the development of improved mechanical-plasmonic sensor microarrays in the near future.

In silico study of substrate chemistry effect on the tethering of engineered antibodies for SARS-CoV-2 detection: Amorphous silica vs gold

“…2 a. Furthermore, the latter value is in agreement with that obtained for pristine IgG1 B12 immobilized on silica (α = 66º) [76] , indicating that the incorporation of the Fab of CR3022 in the engineered antibody does not affect to the orientation with respect to the substrate.…”

Non-covalent Fc-Fab interactions significantly alter internal dynamics of an IgG1 antibody

“…al. where they studied the dynamics of 1HZH tethered to a silica surface using molecular dynamics simulations did not show the pronounced asymmetry observed in our simulations 10 . Identical asymmetric Fab dynamics was also observed in simulations of glycosylated-1HZH in explicit solvent conditions, thus confirming the validity of our simulations.…”

“…While this is true for most conformers, non-covalent interactions between Fc and Fab can lead to more complex free energy profiles which in turn can alter the internal Ab dynamics. Particularly, the presence of Fc-Fab interaction in the human IgG1 b12 structure (pdb id: 1HZH) has been noted in multiple studies 5 , 6 , 10 , 11 . However, the effect of these interactions on the dynamics of the Ab has not been studied in detail.…”

IgG1-b12–HIV-gp120 Interface in Solution: A Computational Study

“… 5 , 6 Similarly, an in-depth understanding of the binding mechanism of broadly neutralizing HIV antibodies would aid the development of new or modified monoclonal antibodies (mAbs) to fight HIV, 7 as well as the development of novel immunosensors with lower production costs and earlier detection windows. 8 , 9 …”

“…5,6 Similarly, an in-depth understanding of the binding mechanism of broadly neutralizing HIV antibodies would aid the development of new or modified monoclonal antibodies (mAbs) to fight HIV, 7 as well as the development of novel immunosensors with lower production costs and earlier detection windows. 8,9 Host cell infection by the primate immunodeficiency viruses primarily occurs through the binding of the viral gp120 envelope glycoprotein to the host's CD4 glycoprotein. 10 Considering this entry point, researchers focused on developing a vaccine that could elicit antibodies that bind to the viral surface-exposed envelope glycoprotein (Env), and thus block the initial stage of infection of the host cells.…”